Peritransplant Deoxyspergualin in Islet Transplantation in Type 1 Diabetes and Extended Follow Up after Islet Transplantation in Type 1 Diabetes (CIT-03/08)

General Description

The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population was individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. The focus of CIT03 was to evaluate the investigational agent, deoxyspergualin. Subjects in CIT03 received rabbit anti-thymocyte globulin (ATG; basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable), deoxyspergualin, etanercept, sirolimus, and low-dose tacrolimus in an open-label fashion.

Objectives

CIT-03: The primary objective of this protocol is to assess the safety and efficacy of an immunosuppressive regimen consisting of ATG (1st transplant only), basiliximab (subsequent transplants only), etanercept, DSG, sirolimus, and low-dose tacrolimus on post-transplant islet function in subjects with T1D.

CIT-08: The primary objective is to provide extended follow-up for safety and efficacy and to support continued islet graft function to participants previously enrolled in CIT02, CIT03, CIT04, CIT05, CIT06, or CIT07.

Outcome Measure

The primary outcome measure was the proportion of participants with insulin independence at 75 days following the first transplant infusion. Secondary outcome measures included reduction in insulin requirements, mean amplitude of glycemic excursions, HbA1c levels, incidence of immune sensitization (defined by detected anti-HLA antibodies not present prior to transplantation), and quality of life.

Criteria

Individuals who met the following criteria were eligible for enrollment:

• Clinical history compatible with type 1 diabetes with onset at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
• Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test
• Involvement of intensive diabetes management, defined as: (1) Self-monitoring of glucose values no less than a mean of three times each day averaged over each week; (2) Administration of three or more insulin injections each day or insulin pump therapy; (3) Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three evaluations during the 12 months prior to study enrollment
• At least one episode of severe hypoglycemia in the 12 months prior to study enrollment
• Reduced awareness of hypoglycemia.

Exclusion criteria are documented in the study protocol.

Outcome

This study has been concluded, but results have not yet been published.